Psychosocial Issues in ART and HIV Preventionthefenwayinstitute.org/wp-content/uploads/8-Safren...84% (self-report diaries) 95% (DOT; 87% of study) 49% CAPRISA 004 1% TDF gel High-risk

Psychosocial Issues in ART and HIV Prevention

Steven A. Safren, PhD

MSM, Mental Health, and Sexual Health1. Why is behavioral

science important when using ART as prevention?

2. How can we address the psychosocial context when looking at HIV risk and self-care? - Examples from successful ART for prevention trials.

The Effects of “Syndemics”on HIV Risk in MSM Cross sectional household telephone survey of MSM in Chicago,

LA, New York ,and SF (N = 2881) High occurrence and interconnectedness of depression, poly drug

use, childhood sexual abuse, and partner violence Additive effects: Odds ratios increased as did number of these

psychosocial health problems

Stall R. American Journal of Public Health. 93:939-942.

1problem

2 problems

3 and 4 problems

High risk sex (P <.01) 1.6 2.4 3.5

HIV prevalence(P <.001)

1.8 2.7 3.6

Example frequent set of Syndemics…

Mental ill-health

Instability Homelessness

Substance Use

Incarceration

Mental health problems when considering optimizing secondary prevention

Condition % Screening Positive (95% CI)*HCSUS (N=2864)HIV-infected

NHSDA (N=22181)Comparison

Major Depression 36.0 (33.6-38.3) 7.6Dysthymia 26.5 (23.5-29.5) ---Generalized Anxiety Disorder 15.8 (14.0-17.7) 2.1

Panic Attack 10.5 (8.0-13.0) 2.5No drug use 49.9 (46.0-53.71) 89.7Marijuana use only/ no dependence

12.1 (10.2-14.8) ---

Other drug use/ no dependence 25.6 (22.1-29.1) ---Drug dependence 12.5 (10.2-14.8) ---

Bing et al., 2001; Archives of General Psychiatry

• 95 independent samples• Depression significantly associated with non-

adherence (p < .0.00001; r = 0.19: CI: .14 - .25)• Adherence via interview versus self-report higher

association• Continuous measures versus dichotomies higher• Not limited to those with clinical depression

• Systematic Review• Active drug use = worse HAART

outcomes (former DU, OST or support = better outcomes)

• Meta analysis:• 38 studies; 14,960 patients• Drug users mean adherence 60%• Comparable to meta analysis of PLWH

in N. America, reporting 55% (overlapping CIs; Mills et al., 2006)

Mental Health / Substance Use Can Interfere with Health Behavior Intervention Models

Information

Behavioral Skills

Motivation

Health behavior / Adherence

Depression / Anxiety, poverty, poor social conditions substance use dx

IMB model from Fisher et al, Health Psychology, 2006.

Initial ART Adherence Intervention Trials

Minimal interventions – MGH/Fenway work “Life-Steps” – single session adherence intervention;

significant effects but comparison group “caught up” over time (Safren et al., 2001)

Pager study – significant but modest effects (Safren et al., 2003)

Meta analyses of adherence interventions: significant but modest effects Simoni (2006): 19 RCTs Amico (2006): 25 studies

Safren et al., 2001, Behaviour Research and Therapy; Safren et al., 2003; AIDS Care; Amico et al., 2006. JAIDS; Simoni et al., 2006. JAIDS

CBT-AD Overview

Modules: 12 sessions, each 50 minutes long

Each CBT module for depression integrates adherence counseling1. Psychoeducation and Motivation………... 1 session

2. Adherence Training / Life-Steps…………. 1 session

3. Behavioral Activation …………………… 2 sessions

4. Adaptive thinking (cognitive restructuring).4 sessions

5. Problem Solving……………………………2 sessions

6. Relaxation Training……………………….. 1 session

7. Maintenance & Relapse Prevention…….. 1 session

Initial Outcome of CBT-AD MEMS outcomes, ITT

0

25

50

75

100

BASELINE T2CBT ETAU

HAM-D outcomes, ITT

0

5

10

15

20

25

BASE T2

CBT ETAU

CGI outcomes, ITT

0

1

2

3

4

5

BASE T2

CBT ETAU

F(1,42) = 21.94, p< .0001, Cohen d = 1.0

Note: effect size conventions .5 = medium, .8 = large, calculated with change scores

F(1,42) = 6.32, p < .02, Cohen d = .82 F(1,42) = 9.68, p < .01, Cohen d = .91

Significant acute improvement in adherence (MEMS) and depression in intent-to-treat analyses

Similar pattern of results for completer analysesThose who “crossed-over” caught up Intervention-associated improvements were generally maintained at 6

and 12 months

54%

88%

54%

62%16.8

13.3

20.4

18.1 3.7

2.83.8

4.0

Safren et al., 2009 – Health Psychology

CBT for adherence and depression in HIV-infected IDU (N=89): Acute outcomes

Depression: Pre-Post Treatment: Significantly greater improvements in depression in treatment versus control condition [MADRS (F(1,79)=6.52, p<.01)] (replicated with clinical global impression [(F(1,79)=14.77, p<.001)] )

65

70

75

80

85

MEM

S Ad

here

nce

(%) P

ast W

eek

15

17

19

21

23

25

27

29

31

Pre Randomization Post Treatment

ControlCBT-AD

MEMs based adherence – above: HLM analysis of MEMs Weeks 0-10 = greater improvement in treatment versus control condition (slope = 0.887, t(86)= 2.38, p = .02)

Safren et al., 2012– JCCP

Outcomes after intervention discontinuation (6 and 12 month)

• Depression: gains were maintained

Safren et al., 2012 – JCCP

5055606570758085

Post Treatment 6 Month F/U 12 Month F/U

ME

MS

Adh

eren

ce

(%) P

ast 2

Wee

ks

CBT-AD

ETAU

• Viral load: No differences across conditions• CD4: the CBT-AD condition had significant

improvements in CD4 cell counts over time compared to ETAU (γslope= 2.09, t (76) = 2.20, p = .03)

• 61.2 CD4 cell increase intervention condition• 22.4 CD4 cell decrease control condition

• MEMs based adherence: gains not maintained

HPTN052 Prevention: 13 Sites, 9 Countries, 1763 serodiscordant couples:Gaborone, Botswana; Kisumu, Kenya; Lilongwe and Blantyre, Malawi; Johannesburg and Soweto, South Africa; Harare, Zimbabwe; Rio de Janeiro and Porto Alegre, Brazil; Pune and Chennai, India; Chiang Mai, Thailand; and Boston

Major finding (Cohen et al., NEJM 2011):

• Early ART prevents HIV transmission in sero-discordant heterosexual couples (1 infection in the early ART arm, 27 infections in delayed)

Major findings (Campbell et al., 2012; PLOS Medicine):

•QD PI regimen (ATV+DDI+EC+FTC) inferior to BID standard of care (EFV+3TC/ZDV) NRTIs + NNRTI

•QD NNRTI regiment (EFV+FTC/TDF) had similar efficacy to standard of care (EFV+3TC/ZDV)

ACTG5175 – TREATMENT 1,571 (201 from U.S.) participants, 9 countries, 4 continents, 3-arm non-inferiority trial: Rio de Janeiro and Porto Alegre, Brazil; Port-au-Prince, Haiti; Chennai and Pune, India; Blantyre and Lilongwe, Malawi; Lima, Peru; Durban and Johannesburg, South Africa; Chiang Mai, Thailand; Harare, Zimbabwe and 31 United States sites

ART for HIV Treatment versus HIV Prevention

OR 95% CI p-value

Week 1.015 (1.008, 1.021) <0.0001

QOL_health 0.991 (0.986, 0.996) 0.0001Treatment <0.0001

1-once daily NRTIs + PI 0.651 (0.518, 0.818) 0.0002

2-once daily NRTIs + NNRTI 0.491 (0.388, 0.621) <0.0001

3-twice daily standard of care 1.000

Region <0.0001

Latin America/Caribbean 1.023 (0.736, 1.443) 0.891

Asia 0.877 (0.618, 1.245) 0.464

Africa 0.520 (0.366, 0.739) 0.0003

United States 1.0001Model includes random intercept (covariance=unstructured)

ACTG 5175 (treatment trial): Significant Multivariable Risk Factors of Pill Count Non-Adherence

HPTN052 (prevention trial): Longitudinal multivariable model: Significant Odds Ratios for 100% Pill Count Adherence

Overview of adherence and efficacy of major PrEP clinical trials

Trial name PrEP formulation Population N Estimated adherence HIV reduction rate

Partners PrEP TDF tablets FTC/TDF tablets

Serodiscordant couples 4,758 97% (clinic pill count)

82% (drug concentration) 67% (TDF)

75% (FTC/TDF)

TDF2-CDC FTC/TDF tablets Heterosexual men and women 1,200 84% (clinic pill count) 63%

iPrEx FTC/TDF tablets MSM 2,499 95% (self-report)

89–95% (clinic pill count) ~50% (drug concentration)

44%

Bangkok Tenofovir Study TDF tablets Injection drug

users 2,413 84% (self-report diaries) 95% (DOT; 87% of study) 49%

CAPRISA 004 1% TDF gel High-risk women 889 72.2% (returned applicators) 39%

FemPrEP FTC/TDF tablets High-risk women 1,951 95% (self-report) <50% (drug concentration)

Study stopped for futility

VOICE TDF, FTC/TDF tablets; 1% TDF gel

Women in high prevalence areas 5,029 90% (self-report)

<30% (drug concentration)

TDF tablets and gel stopped for futility;

FTC/TDF tablets NS

Slide courtesy of Jessica Haberer

The adherence-efficacy relationship

CAPRISA:

iPrEX: HIV risk reduction was 99% when PrEP is taken 7 days a week (modeling data)

Partners PrEP: HIV risk reduction was 90% if TDF/FTC was detectable

Bangkok: HIV risk reduction was 74% if TDF was detectable

Adherence HIV risk reduction>80% 54%

50-80% 38% <50% 28%

Slide courtesy of Jessica Haberer

Partners in PrEP Ancillary Adherence Substudy 3 Study sites in Uganda Adherence monitoring: Intervention 

“triggered” by low (<80%) unannounced pill count adherence Monthly contact with interventionist Number of sessions tailored and variable Optional couples session (s)

Intervention based on “Life‐Steps” (Safren et al., 1997; 2001; 2007) Utilized principles of cognitive behavioral 

therapy (e.g., problem solving and motivational interviewing)  

Standardized provision of information while still tailoring counseling messages to individual needs (12 modules)

Designed to allow delivery by a variety of study staff members with various levels of training

Partners in PrEP Ancillary Adherence Substudy Results HIV Infections 14 in 404 participants on placebo

(333 person-years) 0 infections in 750 participants

on active drug (616 person-years)

PrEP efficacy within this adherence sub-study was 100% (95% CI 83.7-100%, p<0.001)

Partners in PrEP Intervention Characteristics

Median number of sessions = 10 (IQR range = 5‐16)

Median session length  Session 1 = 40 minutes (IQR 30‐50) Length decreased to median 20 minutes (IQR 15‐30) by session 4

Most frequently endorsed barriers to adherence at Session 1: Travel 49.0% Forgetting 44.0% Remained most frequently endorsed barriers across all sessions.

Optimizing PrEP Adherence in MSM: Fenway Project “Prepare”• Intervention content

• CBT-oriented adherence problem-solving skills• brief motivational interviewing• sexual risk-reduction strategies.

• Optional modules• mental health and substance-use barriers to

adherence.

Optimizing PrEP Adherence in MSM: Fenway Project “Prepare”

• Intervention content (based on LifeSteps)• CBT-oriented adherence problem-solving skills• brief motivational interviewing• sexual risk-reduction strategies.

• Optional modules• mental health and substance-use barriers to

adherence.

Project PrEPare: Real Time Assessment of Sexual risk and PrEP Adherence

• Early experience with first set of participants:

• High adherence

• Continued self-reported sexual risk

Optimizing PrEP Adherence in MSM: Fenway Project “Prepare”

SummaryExperience with ART for treatment = adherence

is complicated Interventions to promote adherence need to take into

consideration psychosocial context of nonadherence Next steps: Interventions addressing syndemics in

those with high risk and uncontrolled virusExperience with ART as prevention Failed trials = failed adherence Our experience in Boston = continued risk and

continued high adherence in high risk MSM on PrEP Consistent with iPrEX U.S. data Next steps: Interventions for those with non-

adherence but interest in taking PrEP likely also will need to address the psychosocial context